Psoriasis, a chronic inflammatory skin disorder, is characterized by a complex interplay among immune cells. Although the specific mechanisms of platelet involvement in psoriasis are not fully elucidated, platelet activation is considered a major pathogenic factor. In this study, we investigated the role of Cathelicidin-HG (Cath-HG), a peptide derived from Hylarana guentheri skin that exhibits potent inhibitory activity against platelet glycoprotein VI (GPVI), in an imiquimod-induced psoriasis mouse model. Our experimental findings demonstrated that Cath-HG significantly alleviates psoriasis symptoms, reduces platelet-neutrophil complexes (PNCs) formation, and attenuates neutrophil activation at lesion sites. In vitro studies confirmed that Cath-HG inhibits collagen-induced platelet activation via GPVI, thereby disrupting PNCs formation and suppressing subsequent inflammatory responses. These findings not only establish GPVI as a key regulator of PNC-mediated inflammation in psoriasis but also identify Cath-HG as a promising therapeutic candidate. This study provides a novel mechanistic insight into platelet-neutrophil interactions in psoriasis and highlights the potential of GPVI as a therapeutic target for innovative psoriasis treatments.